Fetal growth and autoimmune thyroid disease

To determine whether fetal and infant growth could influencesusceptibility to autoimmune disease in adults, the occurrenceof thyroid autoantibodies and autoimmune thyroiditis was studiedin 305 women, aged 60–71, born in Hertfordshire and forwhom details of birth weight, infant growth, and feeding wereroutinely recorded. Thyroglobulin autoantibody was detectedin 37% of the women, thyroid peroxidase autoantibody in 41%,and autoimmune thyroiditis, defined as biochemical or clinicalhypothyroidism in association with thyroid autoantibodies, in5.6%. The proportion of women with thyroglobulin and thyroidperoxidase auto antibodies fell with increasing birth weightbut was not related to weight at 1 year of age or the methodof infant feeding. The prevalence of both autoantibodies rosewith increasing adult body mass index but fell as the waistto hip ratio increased. These results demonstrate the importance of early environmentin determining the susceptibility to autoimmune thyroid disease.The contrasting effects of adult body mass index and waist tohip ratio on antibody prevalence could be explained by theirassociations with different hormonal environments.     

Uncertainty in Fitted Estimates of Apparent in Vivo Metabolic Constants for Chloroform

It has become common practice to rely on fitted estimates ofapparent in vivo metabolic constants (e.g., V_max and K_M) inparameterization of PBPK models. Yet, quantitative estimatesof precision in these fitted parameters are not routinely reported.Such information is needed to assess the reliability of modelpredictions. The purpose of this study was to assess the precisionin estimates of V_max and K_M for chloroform, accounting for boththe statistical uncertainties in parameter estimates from individualdata sets and any additional uncertainty due to differencesin the parameter estimates derived from various experiments.Joint confidence regions for V_max and K_M from each experiment,generated using maximum likelihood techniques, were used toevaluate these questions. Three previously published data setswere considered. Estimates of V_max and K_M obtained from thesedata sets differed more than could be explained as a consequenceof a limited number of observations, measurement error, or stochasticerror. Issues associated with the use of maximum likelihoodtechniques to estimate joint confidence regions, the estimationof metabolic constants from individual experiments within agas uptake study versus the full data set, the degree of overlapin the joint confidence regions for metabolic constants obtainedfrom separate data sets, and the implications for risk assessmentare discussed.     

Clinical experience with the use of rhG‐CSF in secondary autoimmune neutropenia

This paper outlines the impact of granulocyte‐colony stimulating factor (G‐CSF) used as a single modality therapy in 17 patients with secondary autoimmune neutropenia (S‐AIN) who had been treated a multiple number of times previously. Fifteen of these patients had demonstrable antineutrophil antibodies and two had cellular S‐AIN with haemopoietic inhibitory T‐cells present in the marrow. Prior to treatment, all had had problems with infection. All patients responded within 7 days of commencement of treatment. Provided G‐CSF neutrophil counts were maintained above 1 × 10⁹/l, no further infections occurred. This was achievable by using G‐CSF administered as infrequently as once every 8 days. Eight of the 17 patients remained on G‐CSF, although five switched to the glycosylated form because of side‐effects. None have developed osteoporosis despite 47.29 patient years of total experience with G‐CSF. In conclusion both glycosylated and nonglycosylated G‐CSF can be used effectively in treating AIN on a long‐term basis.